Breath-activated metered-dose inhaler

ABSTRACT

The invention provides a device for dispensing medication in the respiratory system, with provision for breath-activation; open and closed-mouth technique; recording and control of dosage; and enhanced atomization of liquid medication. This is accomplished with a device that uses a medication canister with an integral battery and circuitry, the battery providing power for electro-mechanical activation, counting medication dosage used or remaining, and controlling device activation. The invention has capability for use with dry and wet medication, and is easily cocked with a simple manual action.

This is a divisional of prior application Ser. No. 09/099,362, now U.S.Pat. No. 6,260,549 file Jun. 18, 1998.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a device for dispensing medication in therespiratory tract, and more particularly to a breath-activated devicewith provision for open and closed-mouth techniques, electronicmeasurement and control, and electro-mechanical activation.

2. Background

Asthma is a disease that is a growing epidemic in this country, andaffects 14.6 million Americans, including 5 million children. (Cowley,G., and Underwood A., Why Ebonie Can't Breathe, Newsweek, May 26, 1997,129(21), 58-64). According to the American Lung Association, the numberof sufferers has risen by 61 percent since the early 1980's. Id. Thedeath toll from asthma has also nearly doubled, to a tragic 5000 peryear. Id. These statistics are appalling considering that today,physicians have many more types of medications available for treatment.

The majority of medications for asthma treatment are intended fordelivery to the lung. In this way, the drug can most quickly reverse theacute breathing problem that asthma causes to the sufferer. Delivery ofmedication directly to the lung also allows use of less drug, minimizingsystemic side effects, since only the lung is affected by the disease.

Techniques of medication delivery to the lungs for asthma sufferers havea long history and have seen many improvements. However, significantdisadvantages remain in the delivery systems in use today. Thenineteenth century saw the invention and use of the glass bulbnebulizer. (Hampson N. B., Mueller M. P., Reduction In-Patient TimingErrors Using A Breath-Activated Metered Dose Inhaler, Chest, August1994, 106(2), 462-465). At the turn of the century, cigarettes lacedwith atropine were used. Id. The first pressure metered dose inhaler(MDI) was introduced in 1956. (Newman S. P., Weisz A. W., Talaee N.,Clarke S. W., Improvement Of Drug Delivery With A Breath-ActivatedPressurized Aerosol For Patients With Poor Inhaler Technique, Thorax,1991, 4(46), 712-716). Though bulky, noisy and cumbersome to use, thefirst breath activated aerosol inhaler was introduced a number of yearsago. Id. In an effort to improve medication delivery, spacer devicesused with MDI's were introduced in the 1970'2. (Iula, A. K., Flynn C.L., Delucca F., Comparative Study Of The In Vitro Dose Delivery AndParticle Size, Distribution, Characteristics Of An Azmacort Metered-DoseInhaler In Combination With Four Different Spacer Devices, CurrentTherapeutic Research, August 1997, 58(8), 544-554).

Nebulizers have been the treatment mainstays for acute asthmatics inemergency department. Nebulizers offer an advantage of delivery a higherdose of medication to the lung than MDI's (Newman S. P., Sted K. P.,Resader S. J., Hooper G., Zierenberg B., Efficient Delivery To The LungsOf Flunisolide Aerosol From A New Portable Hand-Held Multi-DoseNebulizer, Journal of Pharm. Science, September 1996, 85(9), 960-964)and once set up the nebulizer requires no training and minimalcooperation from the patient. With a neubulizer, there is also lessdeposition of medication in the oropharynx as compared to MDI's.(Battistini A., The Best Way To Apply Aerosol Therapy, Pediatric Med.Chir, March-April 1995, 17(b 2), 97-103). The deficiencies of nebulizersare that they are expensive, time consuming, bulky, non-portable, andusually AC current-dependent. A nebulizer also takes minutes to deliverits dose, and needs considerable time to set-up for that delivery. Theoutput of nebulizers is device-dependent and there is significantinter-nebulizer and intra-nebulizer output variance. (NationalInstitutes of Health: National Heat, Lung, and Blood Institute.Guidelines For The Diagnosis And Management Of Asthma, July 1997,Bethesda, Md., NIH Publication No. 97-44051, 1-154).

Another treatment technique uses dry powder medication as a substitutefor aerosol medication. Children and elderly patients often find drypower inhalers easier to use than MDI's. (Newman S. P., Weisz A. W.,Talaee N., Clarke S. W., Improvement Of Drug Delivery With ABreath-Activated Pressurized Aerosol For Patients With Poor InhalerTechnique, Thorax, 1992, 4(46), 712-716). It is reported that inhalerinduced symptoms are lower with some dry powder inhalers (dry powderbudesonide and turbutan) as compared to MDI's. (Pauwels R. A., HargreaveF. E., Camus P., Bukoski M., Stahl E., A 1-Year Study of Turbohaler VsPressurized Metered Dose Inhaler In Asthmatic Patients, Chest, July1996, 110(1), 53-57). Certain dry powder inhalers are also reported todeliver more drug to the lungs than an equivalent aerosol inhaler(Borgstrom L., Derom E., Stahl E., Wahlin-Boll E., Pauwels R., TheInhalation Device Influences Lung Deposition And Bronchodilating EffectOf Terbutaline, American Journal of Respiratory and Critical CareMedicine, May 1996, 153(5), 1636-1640). However, another study reportedthat dry powder inhalers deliver only 10% of the inhaled medication doseto the lungs. (Taburet A. M., Schmidt B., Pharmacokinetic OptimisationOf Asthma Treatment, Pharmacokinetics, May 1994, 26(5),396-418/published erratum in August 1994, 27(2), 149)

Currently, there are also breath activated dry powder inhalers on themarket. Dry powder breath activated inhalers do not rely on coordinationbetween activation and inhalation and therefore are easier for thepatient to use. However, existing dry powder inhalers, including breathactivated devices, have a number of disadvantages. The medication doseis lost if a patient exhales through the device (National Institutes ofHealth: National Heart, Lung, and Blood Institute, Guidelines For TheDiagnosis And Management Of Asthma, July 1997, Bethesda, Md., NIHPublication No. 97-44051, 1-154). It is also necessary to inhale rapidlyto use a dry powder inhaler properly. Id. Rapid inhalation may not bepossible during an acute asthma exacerbation (Boulet L. P., d'Amours P.,Berube D., Rouleau M., Parent J. G., Pelletier C. & Touchette C., UpdateOn Inhalation Therapy In Asthma And Obstructive BronchopulmonaryDiseases, Union Med. Canada, January 1994, 123(1), 23-31§). Thus,inspiratory flow may not be sufficient when medication is most needed.

Devices that do not rely on patient inhalation technique have anadvantage in medication delivery for asthmatics. Spacers are one suchdevice that is being promoted as a way to deliver aerosol from MDI's tothe patient's lung without the need for skillful patient technique.Spacers used with MDI's also offer an advantage to MDI's alone in thatless medication is deposited in the oropharynx, reducing local sideeffects. (National Institutes of Health: National Heart, Lung, and BloodInstitute. Guidelines For The Diagnosis And Management Of Asthma, July1997, Bethesda, Md., NIH Publication No. 97-44051, 1-154). Larger volumespacers (>600 cc) increase lung delivery in MDI's in patients with poorMDI technique. Id. This is due to the large droplets precipitating outin the spacer holding chambers prior to inspiration.

However, spacers also present certain disadvantages. Currently manyspacers are being sold as universal for all aerosol canisters. A studyfound significant differences in the amount of drug available forinhalation when different spacers were used as inhalation aids withdifferent drugs (Barry P. W., O'Callaghan C., Do Multiple Actuations OfSalbutamol MDI Into A Spacer Device Reduce The Amount Of Drug RecoveredIn Respirable Range? European Respiratory Journal, September 1994, 7(9),1707-1709). Spacers can also vary widely as to the amount of respirabledose delivered. (Iula, A. K., Flynn C. L., Delucca F., Comparative StudyOf The In Vitro Dose Delivery And Particle Size, Distribution,Characteristics Of An Azmacort Metered-Dose Inhaler In Combination WithFour Different Spacer Devices, Current Therapeutic Research, August1997, 58(8), 544-554)

Another major problem with spacers is that multiple actuations into thevolumetric spacer does not linearly increase the amount of drugavailable for inhalation (Barry P. W., O'Callaghan C., Do MultipleActuations Of Salbutamol MDI Into A Spacer Device Reduce The Amount OfDrug Recovered In Respirable Range? European Respiratory Journal,September 1994, 7(9), 1707-1709). The amount of medication withinrespirable particles decreases considerably following multipleactivations into a spacer and with increasing residence times within thespacer before inhalation. (O'Callaghan, C., Cant M., Robertson C.,Deliver Beclomethasone Dipropionate From A Spacer Device: What Dose IsAvailable For Inhalation, Thorax, October 1994, 49(10), 961-964).Therefore, patients who pump repeatedly into a spacer during an acuteattack to get additional medication, may mistakenly receive aninsufficient dose.

Large volume spacers are also bulky, and medication export may bereduced in some devices after cleaning and by sanitization. (BisgaardH., Anhoj J., Klug B., Berg E., A Non-Electrostatic Spacer For AerosolDelivery, Arch. of Dic. Children, September 1995, 73(3), 226-230).Static electricity can also reduce spacer output. Id. Reduction inspacer output therefore may occur during conditions when asthma isexacerbated, such as cold dry weather.

For daily treatment of asthma symptoms, MDI's are the most common andwidely prescribed medication delivery system for inhaled medications forasthmatics. Nearly all asthma sufferers depend on MDI's for diseasecontrol and symptomatic relief. Despite almost universal use of MDI's, ahigh percentage of users incorrectly employ MDI's.

The proper use of MDI's is complicated and requires the user/patient toperform the following steps: activation during early inspiration,adequate inspiratory flow, adequate breath holding and deep inhalation.(Goodman D. E., Israel E., Rosenberg M., Johnston R., Weiss St., DrazenJ. M., The Influence Of Age, Diagnosis, And Gender On Proper Use OfMetered-Dose Inhalers, American Journal of Respiratory and Critical CareMedicine, November 1994, 150(5 Part I), 1256-1261). The most frequentpatient errors include: lack of coordination between activation andinspiration; absence of breath holding; and activation of the aerosol onmore than one occasion during inspiration (Boccuti L., Celano M., GellerR. J., Phillips K. M., Development Of A Scale To Measure Children'sMetered Dose Inhaler And Spacer Technique, Annals of Allergy, Asthma andImmunology, September 1996, 77(3), 217-221). These errors adverselyaffect delivery of aerosol medication to the lower respiratory tract.

Improper inhaler technique and inadequate MDI design can lead to sideeffects from the inhaled medications. Corticosteroid inhalers are knownto cause adrenal suppression in some asthmatic children. (Goldberg S.,Algur N., Levi M., Brukheimer E., Hirsch H. J., Branski D., Kereem E.,Adrenal Suppression Among Asthmatic Children Receiving Chronic TherapyWith Inhaled Corticosteroid With And Without Spacer Device, Annuals ofAllergy, Asthma and Immunology, March 1996, 76(3), 245-238). This sideeffect is more common in patients inhaling directly from MDI's thanthose patients using a large volume spacer. Medication deposited in theoropharynx can lead to irritation, foul taste and thrush, which maycause the patient to avoid using the medication. Spacers/holdingchambers decrease oropharyngeal deposition and reduce potential systemicabsorption of inhaled corticosteroid preparations that have higher oralbioavailability. Without a spacer/holding chamber, approximately 80% ofthe dose from an MDI is swallowed. (National Institutes of Health:National Heart, Lung, and Blood Institute. Guidelines For The DiagnosisAnd Management Of Asthma, July 1997, Bethesda Md., NIH Publication No.97-44051, 1-54). Spacer devices are reportedly useful in reducing localside effects in the oropharynx by decreasing deposits in the oropharynxby at least 90%.

One study reported that although MDI's are the most frequentlyprescribed type of inhaler, at least 50% of patients are unable to usethese devices efficiently and 10 to 15% of those patients who caninitially use the MDI efficiently later develop an inefficienttechnique. (Levitt M. A., Gambrioli E. F., Fink J. B., Comparative TrialOf Continuous Nebulization Versus Metered-Dose Inhaler In The TreatmentOf Acute Bronchospasm, Annals of Emergency Medicine, September 1995,26(3), 273-277). Another study showed that only 33.2% of adults and 26%of children used adequate technique (deep inspiration synchronized withinhaler activation, followed by breath holding for 5 seconds). (NationalInstitutes of Health: National Heart, Lung, and Blood Institute.Guidelines For The Diagnosis And Management Of Asthma, July 1997,Bethesda Md., NIH Publication No. 97-44051, 1-154). It was also shownthat almost one half of the patients studied did not activate the MDIcanister at the start of inhalation.

The main factor related to the improper use of MDI's is absence ofprevious instruction. (Benjaponpitak S., Kraisaarin C., DirekwattanachaiC., Sasissakunporn C., Incorrect Use Of Metered Dose Inhalers ByPediatric Residents, Journal of the Medical Association of Thailand,February 1996, 79(2), 122-126). Despite training by the physicians,several studies have demonstrated that may patients do not use MDI's orother inhaler devices correctly, and a simple training session isinadequate. Even with instruction, only 26% of instructed adults and22.1% of instructed children used optimal technique. (Liard R., ZureikM., Aubier M., Korobaaaeff M., Henry C., Neukirch F., Misuse OfPressurized Metered Dose Inhalers By Asthmatic Patients Treated InFrench Private Practice, Rev. Epidemiology Sante Publique, 1995, 43(3),242-249). Unfortunately, instruction of MDI technique requires asignificant time commitment and may not be feasible for all patients,especially those in an Emergency Department. (Selroos O., Lofross A. B.,Pietinaalho A., Riska H., Comparison Of Terbutaline And Placebo From APressurised Metered Dose Inhaler And A Dry Powder Inhaler In A SubgroupOf Patients With Asthma, Thorax, December 1994, 49(12), 1228-1230). Ithas also been demonstrated that the motor/technical skill necessary toproperly use an MDI inhaler can deteriorate over time. (HealthScan, Inc.Chances Are: Handbook of Clinical Probabilities in Asthma. 1997, 11(2)p.1-6; First Quarter)

Physicians themselves have been shown to possess inadequate knowledge ofthe correct use of inhalers with all types of devices (Rebuck D.,Dzyngle B., Khan K., Kesten R. N., Chapman K. R., The Effect OfStructured Versus Conventional Inhaler Education in Medical Housestaff,Journal of Asthma, 1996, 33(6), 385-393). Postgraduate teaching programsleave physicians to acquire inhaler-handling skills informally in thecontext of day-to-day patient care. Id. Many medical personnelresponsible for monitoring and instructing patients in optimal inhalerutilization do not possess rudimentary skills with these devices(Hanania N. A., Wittman R., Kesten S., Chapman K. R., MedicalPersonnel's Knowledge Of And Ability To Use Inhaling Devices: MeteredDose Inhalers, Spacing Chambers, And Breath-Actuated Dry PowderInhalers, Chest, January 1994, 105(1), 111-116). Of seven recommendedsteps for correct MDI use, residents, on average, correctly performedonly 3.8 of these steps. (Amirav I., Goren A., Pawlowski N. A., What DoPediatricians In Training Know About The Correct Use Of Inhalers AndSpacer Devices? Journal of Allergy and Clinical Immunology, October1994, 94(4), 669-675).

In one study, second-year pediatric residents improperly timed theactivation of the MDI 49% of the time, activating the MDI canisterbefore starting inhalation. (Benjaponpitak S., Kraisaarin C.,Direkwattanachai C., Sasissakunporn C., Incorrect Use Of Metered DoseInhalers By Pediatric Residents, Journal of the Medical Association ofThailand, February 1996, 79(2), 122-126). Seasoned physicians do notfare much better. In a survey, only 55% of faculty members correctlyanswered at least three of the seven steps necessary for proper inhalertechnique, though all prescribed MDI's for their patients. (Hira H. S.,Faulty Use Of Metered Dose Inhalers By Physicians, Journal of Assoc. ofPhysicians in India, July 1994, 42(7), 520-525). While educationalsessions may somewhat improve performance, education is not sufficientto guarantee perfect MDI technique. (Resnick D. J., Gold R. L., Lee-WongM., Feldman B. R., Ramakrishnana R., Davis W. J., Annals of Allergy,Asthma Immunology, February 1996, 76(2), 145-148). A single trainingsession using videotaped MDI demonstrations was shown to be inadequatein teaching pharmacists and pulmonary fellows to evaluate MDI technique.(Farr S. J., Rowe A. M., Rubsamen R., Taylor G., Aerosol Deposition InThe Human Lung Following Administration From A Microprocessor ControlledPressurized Metered Dose Inhaler, Thorax, June 1995, 50(6), 639-644)

If physicians and other health care personnel do not know how to useinhalers and have difficult learning proper technique, there is littlechance that they can teach the patients proper technique.

In order to overcome some of the problems with poor MDI technique,aerosol breath activated inhalers are currently available. One suchdevice is shown to require more rapid inspiration to activate than isoptimal for deposition of medication into the lungs. (NationalInstitutes of Health: National Heart, Lung, and Blood Institute.Guidelines For The Diagnosis And Management Of Asthma, July 1997,Bethesda Md., NIH Publication No. 97-44051, 1-154). The device alsoclicks loudly on actuation, and patients may reflexively stop inhalationupon hearing the click, preventing the full dose of medication fromgetting to the lungs. Id.

Optimal design of an MDI for a specific agent also requires precisecalculation based on particle size and other physiochemicalcharacteristics of the particular medication compound as it relates tothe desired dose to be activated from the MDI sprayhead. The respirabledose is commonly defined as total dose with particle size <5.8micrometer. (Iula, A. K., Flynn C. L., Delucca F., Comparative Study OfThe In Vitro Dose Delivery And Particle Size, Distribution,Characteristics Of An Azmacort Metered-Dose Inhaler In Combination WithFour Different Spacer Devices, Current Therapeutic Research, August1997, 58(8), 544-554).

One MDI study showed that firing with a medium inspiratory flow rate (90liters/minute) and early in the cumulative inspired volume (<300 ml)resulted in the highest lung deposition, at 18.6%. (Farr S. J., Rowe A.M., Rubsamen R., Taylor G., Aerosol Deposition In The Human LungFollowing Administration From A Microprocessor Controlled PressurizedMetered Dose Inhaler, Thorax, June 1995, 50(6),639-644). Unfortunately,60% of asthma patients inhale at less than 60 liters/minute, and duringacute attacks their flow rate may be less. (Newman S. P., Sted K. P.,Resader S. J., Hooper G., Zierenberg B., Efficient Delivery To The LungsOf Flunisolide Aersol From A New Portable Hand-Held Multi-DoseNebulizer, Journal of Pharm. Science, September 1996, 85(9), 960-964).Thus, an ideal device needs to be adaptable to fire even with very lowflow rates, because it is at times like these that the asthma patientneeds medication relief most desperately.

In addition to the problems identified above, one study found thatinsufficient hand strength was also a significant cause of the elderlynot being able to use MDI's, which require the patient to apply manualpressure to the top and bottom of the device to activate it. (Gray S.L., Williams D. M., Pulliam C. C., Sirgo M. A., Bishop A. L., Donohue J.F., Characteristic Predicting Incorrect Metered Dose Inhaler TechniqueIn Older Subjects, Archives of Internal Medicine, May 1996, 156(9),984-988). An ideal MDI would require minimal hand strength so that bothchildren and elderly could easily use the device.

Patients often run out of inhaler medication because they can notestimate how much medication remains in the canister. This is becausethey depend on inaccurate methods of estimation, such as shaking theinhalers and listening to the contents, estimating the weight of thecanisters, and observing the size of the emissions.

Rapid serial reactivation of MDI's also reduces respirable dose by 15 to18%. (Everard M. L., Devadason S. G., Summers Q. A., LeSouef P. N.,Factors Affecting Total And “Respirable” Dose Delivered By SalbutamolMetered Dose Inhaler, Thorax, July 1995, 50(997), 746-749). An intervalbetween actuation of at least 5 seconds is considered necessary toconsistently deliver fulls doses. Id.

Additives in MDI's such as inert ingredients including propellant cancause bronchoconstriction in some patients with asthma. (Shaheen M. Z.,Aayres J. G., Benincasa C., Incidence Of Acute Decreaes In PeakExpiratory Flow Following The Use Of Metered Dose Inhalers In AsthmaticPatients, European Respiratory Journal, December 1994, 7(12), 2160-2164)

An open-mouth technique with MDI's, whereby the MDI is manuallyactivated and coordinated with inhalation while the MDI is in proximitybut not in direct contact with the patient's mouth, has been shown tolead to enhanced drug delivery to the lung compared to the conventionalclosed-mouth technique. (National Institutes of Health: National Heart,Lung, and Blood Institute. Guidelines For The Diagnosis And ManagementOf Asthma, July 1997, Bethesda Md., NIH Publication No. 97-44051,1-154). None of the current breath activated inhalers are usable with anopen-mouth technique, however, and the open-mouth technique is difficultto master.

Thus, there are a number of disadvantages that are not addressed bycurrent MDI's, spacers and breath-activated devices.

SUMMARY OF THE INVENTION

It is thus an object of the present invention to provide a device fordispensing medication into the respiratory tract that provides anintegral open-mouth technique position and a closed-mouth techniqueposition.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that providesdifferent air to medication ratios depending on whether the open-mouthtechnique position or closed-mouth technique position is used.

It is a further object of the present invention to provide abreath-activated device for dispensing air-mixed medication into therespiratory tract that provides an electro-mechanical discharge and usesa battery on a disposable canister as the power supply.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that hasfirst and second air-mixing channels.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that has anairflow sensor in a first air channel for sensing inhalation and asecond air channel that is opened during dispensing of the medication.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract thatdispenses liquid medication.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract thatdispenses dry medication.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that has amedication dosage regulator.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that has anindicator of remaining medication dosage, or usage recorder.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that ismanually cocked.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that has asound deadening device acting after breath activation.

It is a further object of the present invention to provide a device fordispensing air-mixed medication into the respiratory tract that has abattery located on or associated with a replaceable medication canisterthat is used to power other functions of the device.

These and other objects of the present invention will be apparent tothose of ordinary skill after review of the specification and claims inview of the figures.

DESCRIPTION OF THE FIGURES

FIG. 1 illustrates one embodiment of the invention in the cockedposition;

FIG. 2 illustrates embodiment of the invention of FIG. 1 immediatelyafter breath-activation;

FIG. 3 illustrates an embodiment of electrical circuitry forelectro-mechanical activation of the device using a crystal flow sensor;

FIG. 4 illustrates an embodiment of the invention providing an openmouth position;

FIG. 5 illustrates an embodiment of the invention providing open andclosed mouth position;

FIG. 6 illustrates an embodiment of the invention providing a bleedhole; and

FIG. 7 illustrates a further embodiment of the invention providing ableed hole.

DETAILED DESCRIPTION

The present invention is a breath-activated inhaler intended to addressthe disadvantages of the previously described MDI's, spacers, andbreath-activated devices. In a preferred embodiment, the device isconstructed primarily of plastic, and includes various electricalcomponents that are battery powered.

Preferably, the invention is electronically activated, and employs amicroprocessor chip, which is integral with each medication canister.The microprocessor chip controls activation based on flow rate and timeinterval from start of inspiration. This allows the same device to beused with different medications but allows each medication to beoptimally delivered.

The invention may also be electro-mechanically activated, using anelectrical solenoid to release a spring mechanism.

The invention may also incorporate an electronic digital counter. Thecounter is part of a replaceable medication canister that has anattached chip and battery power supply to store information on remainingmedication doses. The counter thus provides valuable information to bothpatient and physician, reducing the incidence of patients running out ofmedication. Placing the battery on the replaceable canister also ensuresthat a fresh battery will always be available.

The microprocessor employed in the invention may incorporate a timedelay to prevent rapid successive actuations and thus preventing overmedication. A time delay also serves to discourage patients from“mock-activating” the device with rapid successive actuations.

The invention may also incorporate a bleed hole in the nozzle. Thisfeature, in conjunction with a venturi design, allows more completeatomization of the medication. Smaller droplets (<5 micrometers) can becarried further along a current of air and thus will minimize oropharynxdeposition.

The invention may also incorporate a tube within a tube design in themouthpiece. This two position mouthpiece simulates an open-mouthtechnique using conventional closed-mouth technique. Oropharynxdeposition is decreased with this open-mouth technique. With conventionMDI's, closed-mouth technique requires far less motor skill thanopen-mouth technique. With the present invention, the same technique isused for both closed and open-mouth features. For patients unable togenerate sufficient inspiration flow to trigger the device using thisopen-mouth technique, the patient can put his/her lips around theproximal most part of the mouthpiece to use ordinary closed-mouthinhalation.

The features described above will now be described above in greaterdetail. Referring first to FIG. 1, the invention is illustrated in thecocked, or primed configuration. To operate the device, a cap 101 isremoved and a metered-dose inhaler canister 103 is inserted into anopening. The canister has a nozzle 105 that is directed toward amouthpiece 107. The nozzle of the metered-dose canister is preferablysealed against the bottom of the compartment by a ring gasket 109. Oncethe canister is properly oriented, cap 101 is replaced. Preferably, thecanister has electrical circuitry or microprocessor chip and a battery111 that are constructed so as to form an integral element of thecanister. This has an advantage of providing a fresh battery when thecanister is changed. One function of the circuitry and battery is tooperate the electro-mechanical components of the inhaler whenbreath-activated. This function can be considered to be a medicationdosage regulator in that a dose of medication is only dispensed when theelectro-mechanical components operate. Another function of the circuitryand battery is to collect and record information on how many times thedevice has been used and thereby also determine how many inhalations ordoses remain in the canister. This function can be considered a usagerecorder, as the use information is collected and recorded as the deviceis used or activated. The circuitry that is used to collect and recordinformation on how many time the device has been used can also functionto determine or indicate the remaining medication dosage in thecanister. Canisters are manufactured with a known quantity of medicationand the quantity that is dispensed during each use is also known.Therefore, it is a simple matter to calculate the remaining medicationdosage. It is preferred, but not necessary that these functionsdescribed above be performed.

To place the device in the primed position, as illustrated in theembodiment of FIG. 1, the mouthpiece 107 is extended from the main bodyof the device 112 by holding fingergrips 113 and 115 and pulling themapart until a cantilever latch 117 engages a retainer 119 on themouthpiece. By extending the mouthpiece from the main body and latchingit into that position, a spring 121 is placed in compression. Thecantilever latch 117 is held in the cocked position by another spring123, which also keeps the latch 117 and the retainer 119 properlyoriented. In the figure, the retainer 119 has been illustrated asengaging a v-shaped notch, but other shapes or arrangements that providea positive engagement with an ability to release would be suitable.

In the cocked position, a set of electrical contracts 125 are in contactwith each other, forming an electrically conducting contact, or switch.In this orientation, current may flow through from one contact to theother contact, completing a circuit. In a preferred embodiment, thiscircuit forms part the electro-mechanical circuitry of the device. Inparticular, the contacts 125 may be connected to a flow sensor 127 thatserves to detect inhalation by the patient.

Flow sensor 127 is located in an opening 128 that serves to connect themouthpiece to ambient air. In the cocked position opening 128 is theonly opening between the mouthpiece and ambient air. Thus, when apatient places his or her mouth around the mouthpiece, at position 129,and inhales, all air must flow through the opening 128 and past the flowsensor 127.

When the patient uses the open-mouth position 139 which is described ingreater detail below, less than all the air must flow through theopening 128 and past the flow sensor 127. This is not a problem as theflow sensor has sufficient sensitivity to detect the inhalation flow andactuate the device even when less that all the air flow passes the flowsensor.

In the preferred embodiment, the flow senor 127 is a flow-sensingresistor. In an alternative embodiment, the flow sensor may be a crystalwhose resistance is thermally sensitive. Other alternative embodimentsfor the flow sensor, including but not limited to a mechanical vane andswitch, are also possible and suitable.

After the device is cocked, as described above, the patient holds thedevice by fingergrips 113 in preparation for activation. He then placesthe end of the mouthpiece 107 in his mouth and wraps his lips around theopening at position 129. The patient then simply inhales. As previouslydescribed, when the patient inhales, he draws air through the mouthpieceacross the flow-sensor 127. When the flow sensor is a resistor, the airflow causes the resistor to cool. The reduced temperature causesresistance across the resistor to drop, causing more current to flowacross it according to Ohm's law. Appropriate circuitry senses thischange in current, acting as a switch.

Referring now to FIG. 2, this switching action activates a solenoid 131which moves the cantilever latch 117, releasing the retainer 119, andthereby allowing spring 121 to move mouthpiece 107 relative to the mainbody 112 of the device. When it moves, the end of mouthpiece 107 pushesor depresses the nozzle 105 of the metered-dose inhaler canister 103,releasing aerosolized medication through an opening into the mouthpiece107 where it is then inhaled by the patient, eventually coming to restin the lungs.

In a preferred embodiment, when the solenoid 131 is activated and themouthpiece 107 moves relative to the main body 112 of the device, agated air channel 133 is opened, providing less restriction ofinhalation air flow and allowing a greater quantity of air to be mixedwith the aerosol.

The device has been described thus far with reference to a closed-mouthtechnique. In another embodiment, the device may be used to achieve thebeneficial results of an open-mouth technique. Referring to FIG. 1, asecond mouth position 139 is available. Using this second mouthposition, the patient places his or her lips around an outer tube andinhales. In this second mouth position, an additional air channel 141 isavailable.

Open-mouth technique has been prescribed and used with conventional MDI.Open-mouth technique with a conventional MDI requires the patient tohold the inhaler a few inches from the mouth, and activate the MDI incoordination with inhalation. Using this conventional open-mouthtechnique, the patient inhales additional air, but the amount ofmedication that is deposited in the mouth and oropharynx is less. Whenopen-mouth technique is correctly performed, more medication is carriedto and deposited in the lungs and less medication is deposited in themouth and back of the throat. The mechanism for this improvement inmedication administration is unclear. One possible explanation is thatwith open-mouth technique, the air column that is inhaled is not uniformand the medication is more concentrated in the center of the column. Inthis manner, the medication in the center of the column may be somewhatshielded and therefore less likely to contact the mouth or back of thethroat before being fully inhaled. It is also possible that theadditional air inhaled with open-mouth technique simply alters themedication-to-air ratio and thereby reduces the incidence of medicationdeposit in the mouth or throat. Regardless of the reason, properlyperformed open-mouth technique provides a significant treatmentadvantage. To provide ease of description within this specification, theopen-mouth technique is presumed to result in a differentmedication-to-air ratio than closed-mouth technique.

With a traditional breath-activated device, the use of open-mouthtechnique, where the patient holds the device away from the lips, mightnot provide sufficient flow to actuate the device. However, the presentinvention is more sensitive to flow by using the gated channel. Thus, apatient with poor inspiration flow rate is still able to breath activatethe device using the open-mouth position of the present invention.

It should be noted that while the terms “open-mouth” and “closed-mouth”are used in this description, in both cases, the patient will make lipcontact with the device. This difference is that for the open-mouthtechnique, the patient uses the outer opening 139 and for theclosed-mouth technique, the patient uses the inner opening 129. With aconventional MDI, the only way to perform open-mouth technique is tokeep the lips from contacting the MDI. With the present invention, apatient is able to achieve the beneficial result of an open-mouthtechnique using a device that is operated with the lips contacting themouthpiece as in a closed-mouth device.

Referring again to FIG. 1, in a preferred embodiment, there is also ableed hole 143 in the nozzles 135. The placement of this bleed hole andan accompanying venturi effect provided by a constriction of the airpassage 145, allows air to mix with the medication while in the nozzle,emulsifying the medication before it is ejected from the nozzle 135.This additional air mixing of the medication, while in the nozzle,further ensures that the medication is aerosolized into fine droplets.

In a preferred embodiment, a short time after the device has beendischarged by breath-activation (preferably about 10 seconds), thedevice makes an audible tone, using the circuitry and battery power,signaling to the patient that he can release his breath.

As illustrated in FIG. 2, once the device has been discharged orbreath-activated, the contacts 125 no longer make electrical contact. Inthis “open” position, the contacts can serve to prevent battery drain.Once discharged, no further medicine can be accidentally released untilthe device is cocked or primed again. This “open” or uncocked positionis a storage position for the device.

After each activation, a digital counter shows the number of inhalationsremaining in the canister 103. In a preferred embodiment, the devicealso has a timer delay to prevent a second activation before one minute(or another preset period of time) has elapsed. This time delay allowsthe canister to deliver a full dose in a second activation.

As previously described, it takes only a few seconds to cock the device.Release of the medication into the lungs after breath activation takesmilliseconds.

The device of the present invention is preferably much more sensitive toinhalation than conventional breath-activated devices. This increasedsensitivity is achieved by using the gated channel (133 in FIGS. 1 and2) that opens only after activation. This arrangement allows all airflowto pass over the air flow sensor when in the cocked position and willprovide activation with a flow rate as low as 2 liters/minute. Thiscapability for low flow rate activation can be critical for a patientwith minimal inspiratory flow during an asthma attack.

To prevent the loud click on activation that is heard in the use of somebreath-activated devices, the invention may also include a dashpot 137to dampen the initial motion of the mouthpiece 107 relative to the mainbody 112. The dashpot thus serves as a sound-dampening device to deadenthe sound and reduces noise made during activation.

This device can be manually activated in an emergency in the unlikelycase the batteries on the canister runs out of power or there is anelectronic malfunction. A cover (not illustrated) over the canister iseasily removable to allow manual actuation but a tear sensitive tapewill alert the health professional that the device has been tamperedwith. This, along with the timer delay described above, also discouragesthe practice known as dumping, where the patient repeatedly and rapidlydischarges the MDI, usually just prior to an appointment, in an attemptto hide his or her failure to follow the prescribed medication schedule.

As described above, the device is easy to use, requiring minimal handstrength to cock and only inhalation for activation. This can be veryimportant to persons with arthritis, or to the individual with poorphysical conditioning. The device is also intuitive to use, so thatpatient needs minimal instruction. A simple three-step operation isneeded to use the inhaler: shake, pull out the ends of the inhaler byholding the fingergrips, and then inhale. Electronics allows additionaloptional enhancements such as voice prompts to remind the patient toshake the canister, pull it apart, inhale and when to exhale.

Referring to FIG. 3, an embodiment of an electrical circuit forelectro-mechanical activation is illustrated. The circuit includes aflow sensor 301, and an op-amp 303 to drive a solenoid 305. The contacts125 that are illustrated in FIGS. 1 & 2 are also illustrated. A battery307, to power the device is also illustrated. Parts of the circuitillustrated in FIG. 3, including the battery and op-amp, may be the samechip and battery that is illustrated at 111 in FIGS. 1 & 2.

Though not illustrated, conventional electronic circuitry, as would beknown to one of ordinary skill in the art, are included in theembodiment described above that regulates the medication dosage bymonitoring flow rate and time between start of inspiration. Similarly,circuitry to detect and record usage is included in another embodiment.This circuitry may record each use, subtracting it from a pre-set valueassociated with a full canister and testing the value to see if it hasreached zero. Alternatively, the circuitry may record each use and addit to an initial value then test the value to see if it has reached aspre-set value, representing the total number of doses in the canister.In this manner the circuitry may indicate doses used, or dosesremaining.

Though not illustrated, the conventional electronic circuitry may alsorecord secondary information relating to use, such as date and time ofuse, or time since last use, or any other type of information relatingto use that would help the patient or physician in treatment of thedisease.

As illustrated in FIGS. 1, 2 and 3 the present invention combines anumber of advantages into a single device. However, there are aspects ofthe invention that are adaptable to conventional MDI. For example, FIG.4 illustrates an embodiment of the invention that incorporates theopen-mouth technique with a conventional MDI. In FIG. 4, a conventionalMDI mouthpiece 129 is surrounded by a second mouthpiece 139, whichenables the open-mouth technique. In this embodiment, the patient isonly able to place their lips on the outer mouthpiece and must thereforeuse the device in the open-mouth configuration. By providing an MDI ofthis design, the patent achieves the advantages of open-mouth techniquewith only a slight modification of the conventional MDI.

In another example of the invention, FIG. 5 illustrates a two-positionmouthpiece allowing open-mouth and closed-mouth technique with anotherwise conventional MDI. In this embodiment, a first closed-mouthposition, similar to the mouth position of a conventional MDI, isillustrated at 129. In addition to the closed-mouth position, theinvention also provides an open-mouth position 139. With thiscombination of mouth positions, the invention provides the advantages ofopen-mouth and closed-mouth technique in an MDI that is only slightlymodified.

From the previous examples, it is understood that a two-positionmouthpiece, providing the benefits of open-mouth and closed-mouthtechnique, are accomplished in a number of different embodiments.

In another example of the invention, FIG. 6 illustrates a bleed hole 143that provides enhanced emulsification. This is accomplished with aslightly modified MDI. The combination of bleed hole 143 and venturi145, illustrated in FIG. 6 is readily adaptable to otherwiseconventional MDI and provides better emulsification of the aerosolmedication than is available with conventional MDI. The venturi 145provides an area of low pressure that, in conjunction with the bleedhole 143, ensures greater mixing and emulsification of the medicationthan is available with convention MDI.

FIG. 7 illustrates another embodiment of the present invention where thebleed hole 143 is not closely associated with a structure that isspecifically designed as a venturi, but the relationship between thestructure of the MDI and the bleed hole otherwise provides for pressuredifferentials and thereby allows enhanced emulsification and mixingcompared to that which is available without the bleed hole.

The invention has been described with reference to a number of preferredembodiments with accompanying figures as examples. However, it will beapparent to those of ordinary skill in the art that different aspects orembodiments of the invention may be accomplished independently of eachother and that other embodiments, not expressly described in thespecification, will achieve the objectives of the invention. As such,embodiments that accomplish the objectives of the invention are equallysuitable and are understood to be disclosed by this specification evenif not expressly described in the specification.

I claim:
 1. An apparatus for dispensing air-mixed medication comprising:a mouthpiece having a first tube disposed within a second tube, thefirst tube having a medication discharge passage for discharging amedication, the second tube having ends and a permanent air channeltherethrough such that the air channel does not communicate with thedischarge passage and the air channel communicates with ambient air ateither ends of the second tube; a first air source for air/medicationmixing within the discharge passage; a second air source forair/medication mixing outside the discharge passage and a nozzledisposed within the mouthpiece for receiving a canister containing themedication, the nozzle having a conduit for communication with thecanister and the nozzle defining a bleed hole that is in communicationwith the conduit and ambient air for providing ambient air to theconduit for allowing air/medication mixing in the nozzle.
 2. Theapparatus of claim 1 wherein the medication comprises liquid medication.3. The apparatus of claim 1 wherein the medication comprises drymedication.
 4. The apparatus of claim 1 further comprises a medicationdosage regulator that further comprising circuitry and a battery tooperate electro-mechanical components of the apparatus such that a doseof medication is only dispensed when electro-mechanical componentsoperate.
 5. The apparatus of claim 1 further comprising a usagerecorder.
 6. The apparatus of claim 1 further comprising an indicator ofremaining medication dosage.
 7. The apparatus of claim 1 furthercomprising: a first position on the first tube for facilitatingclosed-mouth technique; and a second position on the second tube forfacilitating open-mouth technique.
 8. The apparatus of claim 7: whereinthe second position provides less oropharynx deposition than the firstposition.
 9. The apparatus of claim 1 wherein the apparatus is activatedby breath activation.
 10. The apparatus of claim 9 further comprising anelectronic sensor for producing a signal in response to a breath. 11.The apparatus of claim 10 further comprising an air flow by-pass fordiverting air around the sensor during medication discharge.
 12. Theapparatus of claim 9 further comprising a mechanical actuator fordispensing the medication, the actuator is manually cocked prior tobreath activation.
 13. The apparatus of claim 9 further comprising asound-dampening device acting after breath activation.
 14. The apparatusof claim 13 wherein the sound-dampening device is a dashpot.
 15. Anapparatus for dispensing air-mixed medication comprising: a main bodyhaving a mouthpiece extending therefrom, the mouthpiece having a firsttube defining a medication discharge passage for discharging amedication and disposed within a second tube, the second tube havingends and a permanent air channel therethrough such that the air channeldoes not communicate with the discharge passage and the air channelcommunicates with ambient air at either ends of the second tube; anozzle disposed within the mouthpiece for receiving a canistercontaining the medication, the nozzle having a conduit for communicationwith the canister and the nozzle defining a bleed hole that is incommunication with the conduit and ambient air for providing ambient airto the conduit for allowing air/medication mixing in the nozzle andoutside of the discharge passage; the first tube defining a constrictionarea adjacent to the nozzle for providing a venturi effect forair/medication mixing within the discharge passage.